Paclitaxel with or without GSK1120212 for treatment of melanoma

ISRCTN	ISRCTN43327231
DOI	https://doi.org/10.1186/ISRCTN43327231
EudraCT/CTIS number	2011-002545-35
Secondary identifying numbers	12095

Submission date: 27/04/2012
Registration date: 27/04/2012
Last edited: 29/01/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-at-gsk1120212-people-melanoma

Contact information

Dr Shama Fernando
Scientific

Oncology Clinical Trials Office
Department of Oncology
Old Road Campus
Roosevelt Drive
Headington
Oxford
OX3 7DQ
United Kingdom

Email	PACMEL@octo-oxford.org.uk

Study information

Study design	Randomised interventional phase II trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	A randomised phase II study of paclitaxel with or without GSK1120212 in advanced wild type BRAF melanoma
Study acronym	PACMEL
Study objectives	This is a randomised multi-centre study. 80 patients (forty in each of 2 arms) with melanoma will be randomly assigned to receive treatment with paclitaxel chemotherapy or the same drug along with GSK1120212, a new medicine. To take part the patient's melanoma must have a normal BRAF gene (at V600), which is about 60% of people with melanoma. This can be checked on a sample of the patient's tumour (usually one that has already been taken as part of their treatment). Prior to the randomised part of the study, between 9 and 18 patients will take part in the trial to establish the best dose of GSK1120212 and paclitaxel in combination.
Ethics approval(s)	NRES Committee South Central - Oxford, 23/01/2012, ref: 11/SC/0458
Health condition(s) or problem(s) studied	Melanoma
Intervention	Dose Escalation Phase: Patients with advanced melanoma will be recruited into 3 dose level cohorts. Three dose levels of GSK1120212, starting at 1.0 mg for the first cohort and escalating by 0.5 mg to 1.5 mg and 2.0 mg for the second and third cohorts respectively. At all dose levels, GSK1120212 will be administered once daily orally in combination with an 80 mg/m2 IV infusion of paclitaxel on Days 1, 8 and 15 of each 4 week cycle. This phase will determine the maximum tolerated dose of GSK1120212 in combination with paclitaxel for the randomisation phase. Paclitaxel will be administered for up to 6 cycles, but GSK1120212 may be continued until disease progression or intolerable toxicity. Randomisation Phase: Two treatment arms: 1. Maximum 6 cycles of single agent Paclitaxel alone as an 80mg/m2 IV infusion on Days 1, 8 and 15 of each 4 week cycle 2. Maximum 6 cycles of Paclitaxel as an 80mg/m2 IV infusion on Days 1, 8 and 15 of each 4 week cycle in combination with maximum tolerated dose of GSK1120212 once daily orally. GSK1120212 may be continued until disease progression or intolerable toxicity. Patients will be followed up every 3 months until disease progression.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	trametinib (GSK1120212), paclitaxel
Primary outcome measure	1. Efficacy of GSK1120212 in combination with paclitaxel compared to paclitaxel alone 2. Progression free survival
Secondary outcome measures	1. Further efficacy of GSK1120212 in combination with paclitaxel compared to paclitaxel alone 2. Overall survival 3. Objectine response rate 4. Progression free survival at 6 months
Overall study start date	13/04/2012
Completion date	30/04/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	UK Sample Size: 98 - a max of 18 patients will be recruited to the dose escalation phase to determine the max tolerated dose. 80 patients will be recruited into the randomised phase II study
Total final enrolment	111
Key inclusion criteria	1. Aged = 18 years 2. Able to provide evidence from an accredited laboratory of wt BRAF status for their melanoma, or ascertainment of wild type BRAF status from a sample of melanoma provided for mutational analysis in Oxford (phase 2 part only). 3. Unresectable stage 3 or 4, histologically proven cutaneous or unknown primary melanoma 4. Measurable disease as defined by RECIST 1.1 (phase 2 part only) 5. ECOG performance score of 0 or 1 6. Life expectancy of at least 12 weeks. 7. Maximum 2 prior lines of treatment for advanced disease. 8. Adequate cardiac function (NYHA 0-1), and LVEF within normal limits on echocardiogram. 9. The patient is willing to give consent to the main study and able to comply with the protocol for the duration of the study, including scheduled follow-up visits and examinations. 10. Adequate haematological, hepatic and renal function 11. Target Gender: Male & Female 12. Lower Age Limit 18 years
Key exclusion criteria	1. Any systemic anti-cancer therapy (including participation in other clinical trials) within 28 days prior to Day 1. 2. Any radiotherapy within 14 days prior to Day 1. 3. Prior taxane or BRAF or MEK inhibitors for metastatic melanoma. 4. Any unresolved toxicity from prior anti-cancer therapy that is greater than CTCAE grade 2. 5. Pregnancy or breastfeeding women. Female patients must have a negative urinary or serum pregnancy test or have evidence of post-menopausal status (defined as absence of menstruation for > 12 months, bilateral oophrectomy or hysterectomy). 6. Grade =2 peripheral neuropathy at study entry. 7. Patients of reproductive potential who are not willing to use adequate contraceptive measures for the duration of the study (both male and female patients) 8. Known severe hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor EL and ethanol 9. Ocular or mucosal malignant melanoma 10. Another active malignancy within the past three years. 11. Evidence of brain metastases, unless surgically resected/stereotactic radiosurgery treated brain metastasis with no evidence of relapse on cerebral MRI, or treated brain metastasis and stable off treatment, including steroids, for 3 months. 12. Clinically significant and uncontrolled major medical condition(s): such as active infection, bleeding diathesis. 13. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV. 14. Inability to swallow tablets, refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease) or significant bowel resection that would preclude adequate absorption. 15. Ocular disease predisposing to central serous retinopathy and/or retinal vein occlusion, including increased intraocular pressure, glaucoma, uncontrolled hypertension or uncontrolled diabetes.
Date of first enrolment	20/04/2012
Date of final enrolment	30/04/2016

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

University of Oxford

Oxford
OX3 7DQ
United Kingdom

Sponsor information

University of Oxford (UK)
University/education

Clinical Trials and Research Governance
Joint Research Office
Block 60
Churchill Hospital
Headington
Oxford
OX3 7LJ
England
United Kingdom

Website	http://www.ox.ac.uk/#http://www.ox.ac.uk/
"ROR"	https://ror.org/052gg0110

Funders

Funder type

Industry

GlaxoSmithKline (UK)
Government organisation / For-profit companies (industry)

Alternative name(s): GlaxoSmithKline plc., GSK plc., GSK
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results				No	Yes
Results article	results for dose escalation phase	01/02/2015		Yes	No
Results article	results	01/02/2019		Yes	No
Results article	results	01/02/2019	29/01/2020	Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

29/01/2020: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
09/04/2019: CRUK link added to the basic results
15/11/2018: Publication reference added.
31/05/2018: Publication reference added.
11/04/2016: No publications found, verifying study status with principal investigator